We have conducted studies aimed to analyze the changes in spinal neural circuits which occur following primary deafferentation, using injection of proteolytic enzymes (pronase) into the sciatic nerve to selectively kill the ganglion cells of that nerve. So far, we have demonstrated several changes within the spinal dorsal horn following pronase injection: 1. Terminal degeneration corresponding to the terminal field of the sciatic nerve. 2. Significant dendritic atrophy and glial response in the dorsal horn 3 weeks following either dorsal rhizotomy or pronase nerve injection. 3. An expansion of small and large diameter saphenous afferents within the dorsal horn, labelled by WGA-HRP and B-HRP, respectively, four months following pronase injection of the sciatic nerve. 4. An increase in the ratio of glomerular to simple saphenous terminals in the expanded area, and an average increase in the number of synaptic contacts made by each saphenous terminal. 5. Significant changes in density of terminals immunoreactive for a variety of peptides found in the dorsal horn. SP and CGRP both show a 20-30% depletion 10-17 days following pronase injection, but a recovery to 15-20% by 6 months. CCK and SS are also reduced in the short term animals, but show little or no recovery after 6 months. These alterations following primary deafferentation of the dorsal horn lead to the hypothesis that there may also be significant changes in receptor binding within the dorsal horn that occur over these same time periods. Alterations in receptor binding in the dorsal horn have been observed previously in several situations, such as experimental peripheral neuropathy or rhizotomy. We now propose to use receptor autoradiography to determine the distribution and density of peptidergic (SP, CGRP, mu, delta and kappa opioid), neurotransmitter (GABA, 5-HT), and excitatory amino acid (glutamate) binding sites in the dorsal horn of short and long term pronase injected animals. In addition to our primary aim to pursue the pronase model, we also will collaborate with Dr. Jerry Collins in his study (project #6) of the roles of propriospinal descending systems in the control of pain and their alteration following discrete spinal lesions. Thus, we will obtain the spinal cord tissue from his experimental cats, and similarly prepare the appropriate segments of spinal cord for receptor autoradiography. Overall, the integration of these studies will allow us to compare the neurochemical reorganization induced by three different, discrete lesions of specific spinal systems, i.e., primary afferents, local propriospinal neurons, and descending brain stem projections.